@article {1016026,
	title = {The Increased Transforming Growth Factor-β Signaling Induced by Diabetes Protects Retinal Vessels},
	journal = {Am J Pathol},
	volume = {187},
	number = {3},
	year = {2017},
	month = {2017 Mar},
	pages = {627-638},
	abstract = {The roles of transforming growth factor (TGF)-β in extracellular matrix production and vascular remodeling, coupled with increased TGF-β expression and signaling in diabetes, suggest TGF-β as an important contributor to the microangiopathy of diabetic retinopathy and nephropathy. To investigate whether increased TGF-β signaling could be a therapeutic target for preventing retinopathy, we used a pharmacologic approach (SM16, a selective inhibitor of the type 1 TGF-β receptor activin receptor-like kinase 5, orally active) to inhibit the increased, but not the basal, Tgf-β signaling in retinal vessels of diabetic rats. At the level of vascular gene expression, 3.5 months{\textquoteright} diabetes induced minimal changes. Diabetes + SM16 for 3 weeks caused widespread changes in gene expression poised to enhance vascular inflammation, thrombosis, leakage, and wall instability; these changes were not observed in control rats\&nbsp;given SM16. The synergy of diabetes and SM16 in altering gene expression was not observed in the lung. At the level of vascular network morphology, 7 months{\textquoteright} diabetes induced no detectable changes. Diabetes + SM16 for 3 weeks caused instead distorted morphology and decreased density. Thus, in\&nbsp;diabetes, retinal vessels become dependent on a small increase in TGF-β signaling via activin receptor-like kinase 5 to maintain early integrity. The increased TGF-β signaling may protect against rapid retinopathy progression and should not be a target of inhibitory interventions.},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2016.11.007},
	author = {Dagher, Zeina and Chiara Gerhardinger and Vaz, Joseph and Goodridge, Michael and Tecilazich, Francesco and Lorenzi, Mara}
}
